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MRC DiMeN Doctoral Training Partnership: Understanding how tissue stiffening affects cancer cell response to therapy


   MRC DiMeN Doctoral Training Partnership

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  Dr Helen Matthews, Dr H Bryant  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Pancreatic cancer has a low survival rate and new therapies are urgently needed. Currently the only treatments available are chemotherapy drugs that non-specifically target DNA replication and cell cycle progression. However, a new class of small molecule inhibitors have recently been developed targeting KRAS, an oncogene mutated in 90% of pancreatic cancers, which offer new promise for targeted therapy. 

One of the reasons that pancreatic cancer is so hard to treat is that tumours are surrounded by extremely rigid, fibrotic extra-cellular matrix (ECM). This altered tumour microenvironment means that tumours are far stiffer than healthy tissue. Tissue stiffening has been shown to promote cancer cell proliferation, invasion and metastasis but also contribute to resistance to therapy.

This 4-year PhD project will investigate how the stiffness of the extracellular environment affects pancreatic cancer cell response to therapy, including standard chemotherapy drugs and new KRAS inhibitors. We will use a variety of cell biology techniques including cell culture, RNA sequencing and cutting-edge microscopy to unpick the molecular details of cells response to therapy. To understand the effects of tissue stiffening, cells will be grown in micro-fabricated chambers where the stiffness and ECM composition can be varied and mechanical forces (such as compression) can be applied.

This is a collaborative project between the Helen Matthews’ (School of Biosciences) and Helen Bryant’s (Dept. of Oncology and Metabolism) groups at the University of Sheffield. Being embedded within both the Biosciences and Oncology departments, this project will provide a broad training in cell and cancer biology and give access to a wide variety of development opportunities, in addition to those provided by the MRC DiMeN scheme. Both the Matthews and Bryant groups are based in shared laboratories that provide friendly, inclusive and supportive environments for our cancer researchers.

Please feel free to contact us if you would like to learn more about the project or research environment. More information on the host labs can also be found on our websites or twitter accounts:

https://www.helenmatthewslab.org/

https://www.sheffield.ac.uk/medicine/people/oncology-metabolism/helen-e-bryant

Twitter: @helenkmatthews @bryantlab1

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: https://www.dimen.org.uk/blog

Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/how-to-apply


Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 4yrs. Funding will cover tuition fees, stipend and project costs. We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of full studentships to international applicants. Please read additional guidance here: https://www.dimen.org.uk/eligibility-criteria
Studentships commence: 1st October 2023
Good luck!

References

Matthews, H.K. et al (2022) Cell Cycle Control in Cancer
Nature Rev Mol Cell Biology. 23, 74–88
https://doi.org/10.1038/s41580-021-00404-3
Grant, E. et al (2022) Progesterone receptor expression contributes to gemcitabine resistance at higher ECM stiffness in breast cancer cell lines. PLOS ONE 17(5): e0268300
https://doi.org/10.1371/journal.pone.0268300
Matthews, H.K. et al (2020) Oncogene activation alters cell shape and mechanics to facilitate cell division in confinement. Developmental Cell. 52, 563-573.
https://doi.org/10.1016/j.devcel.2020.01.004
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